Functional analysis of Scratch2 domains: implications in the evolution of Snail transcriptional repressors

AbstractThe Snail superfamily of transcription factors have a modular organization and their similarities and divergences are the basis for subdividing the superfamily into the Snail1/2 and Scratch families. As it is generally accepted that the Snail and Scratch families originated through gene duplication, understanding the functional contribution of each module could provide us with further insight about the molecular and functional evolution of the Snail superfamily. Thus, in this work, we investigated the function of the SNAG and SCRATCH domains in chicken Scratch2. Through evolutionary comparison analysis we identified a novel HINGE domain that lies between the SNAG and SCRATCH domain. Similar to members of the Snail1/2 families, Scratch2- mediated transcriptional repression requires SNAG and nuclear localization requires the zinc-finger domain. We also identified a novel HINGE domain that lies between the SNAG and SCRATCH domain. HINGE is highly conserved in amniotes. Single mutations of the conserved Tyrosine and Serine residues of HINGE downregulated Scratch2-mediated transcriptional repression. This effect depended on the presence of the SCRATCH domain.

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Binding Sites in theEFG1Promoter for Transcription Factors in a Proposed Regulatory Network: A Functional Analysis in the White and Opaque Phases ofCandida albicans

G3 Genes|Genome|Genetics ◽

10.1534/g3.116.029785 ◽

2016 ◽

Vol 6 (6) ◽

pp. 1725-1737

Author(s):

Claude Pujol ◽

Thyagarajan Srikantha ◽

Yang-Nim Park ◽

Karla J. Daniels ◽

David R. Soll

Keyword(s):

Functional Analysis ◽

Transcription Factors ◽

Binding Sites ◽

Regulatory Network ◽

Ofcandida Albicans

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Genome-Wide Identification of Zn2Cys6 Class Fungal-Specific Transcription Factors (ZnFTFs) and Functional Analysis of UvZnFTF1 in Ustilaginoidea virens

Rice Science ◽

10.1016/j.rsci.2021.03.001 ◽

2021 ◽

Vol 28 (6) ◽

pp. 567-578

Author(s):

Song Tianqiao ◽

Zhang Xiong ◽

Zhang You ◽

Liang Dong ◽

Yan Jiaoling ◽

...

Keyword(s):

Functional Analysis ◽

Transcription Factors ◽

Ustilaginoidea Virens ◽

Genome Wide

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The histone variant H2A.Z and chromatin remodeler BRAHMA act coordinately and antagonistically to regulate transcription and nucleosome dynamics in Arabidopsis

10.1101/243790 ◽

2018 ◽

Author(s):

E. Shannon Torres ◽

Roger B. Deal

Keyword(s):

Transcriptional Regulation ◽

Transcription Factors ◽

Binding Sites ◽

Transcriptional Repression ◽

Nucleosome Positioning ◽

Chromatin Organization ◽

Histone H2a ◽

Nucleosome Dynamics ◽

Environmentally Responsive ◽

Context Specific

ABSTRACTPlants adapt to changes in their environment by regulating transcription and chromatin organization. The histone H2A variant H2A.Z and the SWI2/SNF2 ATPase BRAHMA have overlapping roles in positively and negatively regulating environmentally responsive genes in Arabidopsis, but the extent of this overlap was uncharacterized. Both have been associated with various changes in nucleosome positioning and stability in different contexts, but their specific roles in transcriptional regulation and chromatin organization need further characterization. We show that H2A.Z and BRM act both cooperatively and antagonistically to contribute directly to transcriptional repression and activation of genes involved in development and response to environmental stimuli. We identified 8 classes of genes that show distinct relationships between H2A.Z and BRM and their roles in transcription. We found that H2A.Z contributes to a range of different nucleosome properties, while BRM stabilizes nucleosomes where it binds and destabilizes and/or repositions flanking nucleosomes. H2A.Z and BRM contribute to +1 nucleosome destabilization, especially where they coordinately regulate transcription. We also found that at genes regulated by both BRM and H2A.Z, both factors overlap with the binding sites of light-regulated transcription factors PIF4, PIF5, and FRS9, and that some of the FRS9 binding sites are dependent on H2A.Z and BRM for accessibility. Collectively, we comprehensively characterized the antagonistic and cooperative contributions of H2A.Z and BRM to transcriptional regulation, and illuminated their interrelated roles in chromatin organization. The variability observed in their individual functions implies that both BRM and H2A.Z have more context-specific roles within diverse chromatin environments than previously assumed.

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Transcriptional repression by the Drosophila giant protein: cis element positioning provides an alternative means of interpreting an effector gradient

Development ◽

10.1242/dev.126.6.1201 ◽

1999 ◽

Vol 126 (6) ◽

pp. 1201-1210 ◽

Cited By ~ 3

Author(s):

G.F. Hewitt ◽

B.S. Strunk ◽

C. Margulies ◽

T. Priputin ◽

X.D. Wang ◽

...

Keyword(s):

Transcription Factors ◽

Binding Sites ◽

Transcriptional Repression ◽

Short Range ◽

Initiation Site ◽

Step Function ◽

Drosophila Embryo ◽

Transcriptional Initiation ◽

Cis Element ◽

Alternative Means

Early developmental patterning of the Drosophila embryo is driven by the activities of a diverse set of maternally and zygotically derived transcription factors, including repressors encoded by gap genes such as Kruppel, knirps, giant and the mesoderm-specific snail. The mechanism of repression by gap transcription factors is not well understood at a molecular level. Initial characterization of these transcription factors suggests that they act as short-range repressors, interfering with the activity of enhancer or promoter elements 50 to 100 bp away. To better understand the molecular mechanism of short-range repression, we have investigated the properties of the Giant gap protein. We tested the ability of endogenous Giant to repress when bound close to the transcriptional initiation site and found that Giant effectively represses a heterologous promoter when binding sites are located at −55 bp with respect to the start of transcription. Consistent with its role as a short-range repressor, as the binding sites are moved to more distal locations, repression is diminished. Rather than exhibiting a sharp ‘step-function’ drop-off in activity, however, repression is progressively restricted to areas of highest Giant concentration. Less than a two-fold difference in Giant protein concentration is sufficient to determine a change in transcriptional status of a target gene. This effect demonstrates that Giant protein gradients can be differentially interpreted by target promoters, depending on the exact location of the Giant binding sites within the gene. Thus, in addition to binding site affinity and number, cis element positioning within a promoter can affect the response of a gene to a repressor gradient. We also demonstrate that a chimeric Gal4-Giant protein lacking the basic/zipper domain can specifically repress reporter genes, suggesting that the Giant effector domain is an autonomous repression domain.

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The AP-1 Family of Transcription Factors: Structure, Regulation, and Functional Analysis in Mice

Targets for Cancer Chemotherapy ◽

10.1385/1-59259-153-1:29 ◽

2003 ◽

pp. 29-52

Author(s):

Marina Schorpp-Kistner ◽

Peter Herrlich ◽

Peter Angel

Keyword(s):

Functional Analysis ◽

Transcription Factors ◽

Structure Regulation

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A Phenome-Based Functional Analysis of Transcription Factors in the Cereal Head Blight Fungus, Fusarium graminearum

PLoS Pathogens ◽

10.1371/journal.ppat.1002310 ◽

2011 ◽

Vol 7 (10) ◽

pp. e1002310 ◽

Cited By ~ 177

Author(s):

Hokyoung Son ◽

Young-Su Seo ◽

Kyunghun Min ◽

Ae Ran Park ◽

Jungkwan Lee ◽

...

Keyword(s):

Functional Analysis ◽

Transcription Factors ◽

Fusarium Graminearum ◽

Head Blight

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Transcriptional Regulation of the AP-2α Promoter by BTEB-1 and AP-2rep, a Novel wt-1/egr-Related Zinc Finger Repressor

Molecular and Cellular Biology ◽

10.1128/mcb.19.1.194 ◽

1999 ◽

Vol 19 (1) ◽

pp. 194-204 ◽

Cited By ~ 71

Author(s):

Axel Imhof ◽

Marion Schuierer ◽

Oliver Werner ◽

Markus Moser ◽

Christina Roth ◽

...

Keyword(s):

Transcriptional Regulation ◽

Transcription Factors ◽

Zinc Finger ◽

Transcriptional Repression ◽

Promoter Activity ◽

Zinc Finger Protein ◽

Cdna Expression Library ◽

Neuro2a Cell ◽

Expression Library ◽

Cell Extracts

ABSTRACT AP-2 transcription factors have been suggested to exert key regulatory functions in vertebrate embryonic development, in tumorigenicity of various cancer cell types, and in controlling cell cycle and apoptotic effector genes. In this study, we investigated transcriptional regulation of the AP-2α gene promoter mediated by an autoregulatory element (referred to as A32) with a core consensus AP-2 binding site at position −336 relative to the mRNA initiation site. AP-2 and multiple different nuclear proteins in HeLa and Neuro2A cell extracts form specific bandshifts with the A32 element. By screening a mouse brain cDNA expression library, we isolated two different cDNAs encoding the transcription factor BTEB-1 and a novel zinc finger protein, AP-2rep. AP-2rep reveals a modular structure with homology to transcription factors of the wt-1/egr-1-family. AP-2rep, BTEB-1, and AP-2 interact in a mutually exclusive manner with overlapping binding sites in the A32 element. Transfection studies revealed that BTEB-1 is a strong activator of AP-2α promoter activity, whereas cotransfected AP-2α resulted in moderate autoactivation of promoter activity. In contrast, AP-2rep confers strong transcriptional repression to the AP-2α gene, and we observed an excellent correlation between induction of AP-2rep mRNA expression and downregulation of AP-2α mRNA during development of the kidney. In summary, we have identified multiple transcription factors and cloned from an expression library a novel zinc finger silencing factor, AP-2rep, mediating positive and negative regulation of AP-2α expression through a set of overlappingcis-regulatory promoter elements.

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